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地塞米松预处理对预防急性炎症后认知障碍发展的影响。

Impact of Dexamethasone Preconditioning on Prevention of Development of Cognitive Impairment following Acute Inflammation.

机构信息

Department of Anesthesiology, Tianjin Hospital, Tianjin 300211, China.

Jinnan District Center for Disease Control and Prevention, Tianjin 300300, China.

出版信息

Contrast Media Mol Imaging. 2022 Jun 14;2022:6064007. doi: 10.1155/2022/6064007. eCollection 2022.

Abstract

To assess the preventive role of dexamethasone (Dex) in the development of neuroinflammation and concomitant neurocognitive disorders following acute inflammation. C57BL6 mice were fallen into the sham group, ischemia-reperfusion (/) group, and I/ + Dex group randomly. In the end, behavioral alterations were assessed with the Morris water maze (MWM) test, passive avoidance test (PAT), and open field test (OFT). The serum levels of IL-1 and TNF- were detected by ELISA. Immunofluorescence was adopted to observe the NF-kB expression in the hippocampus. In addition, TLR4, NF-kB, CD68, and CD206 were examined by Western blot. The cognitive ability of mice can be impaired by tourniquet-induced acute inflammation, and these changes were prevented by Dex. Compared to the / group, Dex pretreatment could decrease levels of IL-1 and TNF- proteins in serum. Besides, Dex preconditioning significantly decreased the utterance of NF-kB immunoreactive cells and TLR4, NF-kB, and CD68 overexpression in the hippocampus. Dex partly through inhibiting microglia transformation to the M1 polarization state and inactivating the TLR4/NF-kB pathway attenuates the cognitive disorders in mice.

摘要

为了评估地塞米松(Dex)在急性炎症后神经炎症和随之发生的神经认知障碍发展中的预防作用,将 C57BL6 小鼠随机分为假手术组、缺血再灌注(/)组和 I/ + Dex 组。最后,通过 Morris 水迷宫(MWM)测试、被动回避测试(PAT)和旷场测试(OFT)评估行为改变。通过 ELISA 检测血清中 IL-1 和 TNF- 的水平。采用免疫荧光法观察海马 NF-kB 的表达。此外,通过 Western blot 检测 TLR4、NF-kB、CD68 和 CD206。止血带诱导的急性炎症可损害小鼠的认知能力,而 Dex 可预防这些变化。与/组相比,Dex 预处理可降低血清中 IL-1 和 TNF- 蛋白水平。此外,Dex 预处理可显著减少海马中 NF-kB 免疫反应细胞和 TLR4、NF-kB 和 CD68 的过度表达。Dex 通过抑制小胶质细胞向 M1 极化状态的转化并激活 TLR4/NF-kB 通路,部分减轻了小鼠的认知障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de8/9213130/7228b53bd030/CMMI2022-6064007.001.jpg

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